https://scholars.lib.ntu.edu.tw/handle/123456789/588558
標題: | Targeting endothelium-pericyte cross talk by inhibiting VEGF receptor signaling attenuates kidney microvascular rarefaction and fibrosis | 作者: | SHUEI-LIONG LIN FAN-CHI CHANG Schrimpf C. YI-TING CHEN Wu C.-F. VIN-CENT WU WEN-CHIH CHIANG Kuhnert F. Kao C.-J. YUNG-MING CHEN KWAN-DUN WU TUN-JUN TSAI Duffield J.S. |
公開日期: | 2011 | 出版社: | Elsevier Inc. | 卷: | 178 | 期: | 2 | 起(迄)頁: | 911-923 | 來源出版物: | American Journal of Pathology | 摘要: | Microvascular pericytes and perivascular fibroblasts have recently been identified as the source of scar-producing myofibroblasts that appear after injury of the kidney. We show that cross talk between pericytes and endothelial cells concomitantly dictates development of fibrosis and loss of microvasculature after injury. When either platelet-derived growth factor receptor (R)-β signaling in pericytes or vascular endothelial growth factor (VEGF)R2 signaling in endothelial cells was blocked by circulating soluble receptor ectodomains, both fibrosis and capillary rarefaction were markedly attenuated during progressive kidney injury. Blockade of either receptor-mediated signaling pathway prevented pericyte differentiation and proliferation, but VEGFR2 blockade also attenuated recruitment of inflammatory macrophages throughout disease progression. Whereas injury down-regulated angiogenic VEGF164, the dys-angiogenic isomers VEGF120 and VEGF188 were up-regulated, suggesting that pericyte-myofibroblast differentiation triggers endothelial loss by a switch in secretion of VEGF isomers. These findings link fibrogenesis inextricably with microvascular rarefaction for the first time, add new significance to fibrogenesis, and identify novel therapeutic targets. Copyright ? 2011 American Society for Investigative Pathology. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-79951816985&doi=10.1016%2fj.ajpath.2010.10.012&partnerID=40&md5=46a63bd02c4595af542d8e7d1623417d https://scholars.lib.ntu.edu.tw/handle/123456789/588558 |
ISSN: | 0002-9440 | DOI: | 10.1016/j.ajpath.2010.10.012 | SDG/關鍵字: | antifibrotic agent; platelet derived growth factor beta receptor; soluble platelet derived growth factor beta receptor; soluble VEGF 2 receptor; unclassified drug; vasculotropin receptor 2; animal cell; animal experiment; animal model; animal tissue; article; capillary; cell differentiation; cell interaction; cell proliferation; controlled study; disease course; embryo; endothelium cell; fibrogenesis; human; human cell; innate immunity; intracellular signaling; kidney fibrosis; kidney injury; macrophage migration; microvasculature; molecular interaction; molecularly targeted therapy; mouse; myofibroblast; nonhuman; pericyte; priority journal; protein secretion; receptor blocking; receptor down regulation; receptor upregulation; target cell |
顯示於: | 醫學系 |
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